Medical imaging using X-rays to produce a two dimensional image of internal body structures and detection of disease based on their differential attenuation of X-rays has a long and well documented history. A recent advance in X-ray imaging is computerized tomography (CT) which enables one to produce a tomographic three-dimensional X-ray image with high spatial resolution showing internal structures which might not be easily detected with conventional two dimensional X-ray techniques.
Ionic and non-ionic iodine based contrast enhancement agents are often used with CT to better differentiate between different tissues and compartments and to detect abnormalities. Because iodine has a high atomic number, it absorbs or attenuates X-rays in proportion to its presence. Iodine based contrast enhancement agents are injected intravenously and so their use involves an invasive procedure. The primary use of iodine based contrast enhancement agents is in the diagnosis of disease and appraisal of therapy concerning the arterio-venous (vascular) system, which they improve the visualization of. Iodine based contrast enhancement agents stay in the vascular system unless the wall of the blood vessel(s) is damaged by disease. They do not normally cross the blood-brain barrier. They are also used to detect abnormalities within the blood vessels such as occlusions (blockages).
While CT uses a highly collimated (focused) beam of X-rays, which minimizes radiation dosage to tissues other than those being examined, radiation dosages are still considered to be high and thus it is desirable to have an imaging method which does not use X-rays. This is especially true with pediatric patients.
Recently magnetic resonance imaging (MRI) was commercially introduced to the medical field. MRI is a three dimensional imaging process. It is based on the same underlying principles as nuclear magnetic resonance (NMR), which has been used for some time in analytical chemistry.
MRI is advantageous over two dimensional and three dimensional CT X-ray techniques in that MRI better defines soft tissue structures. It is also advantageous over X-ray techniques, because it does not require the patient being exposed to X-rays. While energy deposition occurs in the patient because magnetism is electromagnetic energy, it occurs in amounts that using currently authorized MRI magnetic field strengths and imaging methodologies are considered very safe.
As with CT, the likelihood of an accurate diagnosis and assessment of therapeutic impact may be improved in MRI by the use of a contrast enhancement agent. The usefulness of an MRI contrast enhancement agent depends on the physical, chemical and biological properties of the agent and how it distributes within the body in normal and abnormal (diseased) states. However, unlike the iodine based contrast enhancement agents used in CT which produce contrast based on the attenuation of X-rays, a contrast enhancement agent useful with MRI will generate a contrast factor, based on how its atomic structure responds to magnetic fields and one or more MRI imaging methodologies.
At present, only gadopentetate dimeglumine, which must be injected and so is invasive, is authorized for use as a contrast enhancement agent with MRI. Gadopentetate dimeglumine is a highly effective relaxation agent and its use has been authorized to provide contrast enhancement when used with MRI in those intracranial lesions with abnormal vascularity or those thought to cause an abnormality in the blood-brain barrier and to facilitate visualization of intracranial lesions including but not limited to tumors. This contrast enhancer is an intravascular agent and cannot cross the blood-brain barrier unless the blood-brain barrier is damaged. It is also authorized for use in the detection of lesions of the spine. However, potential side effects and adverse reactions exist.
Accordingly, it is an object of this invention to provide an improved magnetic resonance imaging method.
It is another object of this invention to provide an improved magnetic resonance imaging method employing a contrast enhancer which overcomes problems associated with heretofore known methods.
It is a further object of this invention to provide an improved magnetic resonance imaging method employing a contrast enhancement agent which provides improved diagnostic and therapy assessment capabilities.
It is a still further object of this invention to provide a contrast enhancement mixture which may be provided to a living organic subject for improving magnetic resonance imaging.